Symptoms of depression among outpatients with suspected COVID-19 in metropolitan Local Government Areas of Kaduna State, Nigeria

Background The novel SARS-CoV-2 virus that causes Coronavirus disease (COVID-19) has redefined global health and response to Acute Respiratory Infection (ARI). The outbreak of a cluster of influenza-like illnesses in Wuhan, China, has morphed into a pandemic in the last quarter of 2019, stretching from South East Asia to Europe, The Americas, Africa, and the Australian subcontinent. We evaluated the prevalence of depression among outpatients diagnosed with ARI. Materials and methods We utilized a cross-sectional, observational design and investigated the prevalence of symptoms of depression among outpatients with ARI and described the characteristics of outpatients with ARI in Kaduna State. Results The prevalence of symptoms of depression was 19.6% for respondents with symptoms of ARI and 14.4% for those without symptoms of ARI. On no risk of depression, we had a higher proportion of the respondents without symptoms of ARI (86%) than those with symptoms of depression (80%) (M = 318.4, SD = 29.62 case, and M = 344.0, SD = 14.2 control, r = 0.88, CI = 13.5 to 6.5, P = 0.000952). Likewise, in the category with mild risk of depression, respondents without symptoms of ARI were fewer (10%) than those with symptoms of depression (15%) (M = 58.4, SD = 26.0 case, and M = 42.1, SD = 12.7 control, r = 0.86, CI = 11.8 to 5.8, P = 0.0136. There was no significant difference between respondents with symptoms of ARI and without symptoms of ARI in the categories of moderate (M = 13.6, SD = 5.1 case, and M = 11.6, SD = 4.6 control, r = 0.87, CI = 2.3 to 2.1, P = 0.178) and high (M = 5.6, SD = 2.5 case, and M = 4.4, SD = 3.2 control, r = 0.61, CI = 1.2 to 1.5, P = 0.174) risk of depression. Conclusion Symptoms of depression were commoner among respondents who presented with symptoms of Acute Respiratory Infection (ARI) at the Outpatient Department (OPD). However, further explanatory research is needed to establish causality.


Introduction
The novel SARS-CoV-2 virus that causes Coronavirus disease (COVID-19) has redefined global health and response to Acute Respiratory Infection (ARI) [1][2][3][4].The outbreak of a cluster of influenza-like illnesses in Wuhan, China, has morphed into a pandemic in the last quarter of 2019, stretching from South East Asia to Europe, The Americas, Africa, and the Australian subcontinent [5].The World Health Organization (WHO) declared COVID-19 a Public Health Emergency of International Concern (PHEIC) in January 2020 and a pandemic in March 2020 [6,7].The statistics are grim, with over 666 million laboratory-confirmed cases and 6 million deaths recorded globally as of 15 th January 2023 [8].Nigeria's first confirmed COVID-19 case was on 14 th February 2020, and has recorded 266, 463 confirmed cases and 3, 155 deaths as of 15 th January 2023 [9,10].Kaduna State, a subnational entity in federal Nigeria, had the first confirmed COVID-19 case on 28 th March 2020, and a total of 11, 630 confirmed cases with 90 deaths as of 15 th January 2023 [9].The four metropolitan Local Government Areas (LGAs) of Chikun, Igabi, Kaduna North, and Kaduna South account for over 50% of all confirmed cases in Kaduna State [9].
Acute Respiratory Infection, like COVID-19, usually presents as cough, sneezing, sore throat, and difficulty breathing, with or without fever, and is transmitted through contact with an infected person or their secretions [11][12][13].Other symptoms are body weakness, loss of smell, diarrhea, abdominal pains, and some non-specific symptoms [14].The prognosis of COVID-19 is worse in the elderly and those with other co-existing conditions, for example, diabetes, hypertension, asthma, and so forth [15].Many COVID-19 cases are asymptomatic, and laboratory test using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and Rapid Diagnostic Test (RDT) is essential in diagnosis and case confirmation [16].Like many low-and middle-income countries (LMIC), Nigeria has low testing rates, making COVID-19 diagnosis difficult and the efforts to contain the pandemic challenging [17].
COVID-19 now has a vaccine, but before vaccine discovery and licensing, the mainstay of response was non-pharmaceutical interventions (NPI), regular handwashing with soap under running water; respiratory hygiene, and coughing into a bent elbow; physical distancing of at least 2 meters; use of face masks; hand sanitizers; environmental sanitation; lockdown and restriction of movements and other administrative measures [18][19][20][21].COVID-19 rollout has not been even, as the high-income countries account for over 80% of current vaccine uptake [22].The COVAX facility, led by the World Health Organization (WHO), Coalition for Epidemic Preparedness Innovation (CEPI), and UNICEF, have supported LMICs, and the COVID-19 vaccine rollout has commenced in Nigeria and other developing countries [23].
The symptoms of depression are common, and a study by Gureje et al. has shown a prevalence of 5% among the general population in major Nigerian cities [24].Case managers at the isolation centres have observed rising symptoms of depression among COVID-19 patients, and Sensoy et al. (2021) documented a significantly higher average level of depression (24%) among COVID-19 patients [25].The cardinal symptoms of depression are low mood, loss of interest in pleasurable activities, and worthlessness.Other symptoms are lack of energy, loss of appetite, body weakness, sadness, suicidal ideation, etc. COVID-19 sometimes manifests with symptoms of depression, which the isolation may worsen, restriction of movements, and lockdown in response to the COVID-19 pandemic [26].
Little or no studies have investigated the prevalence of symptoms of depression among outpatients with ARI nor described the characteristics of outpatients with ARI in Kaduna State.
The response to COVID-19 is a combination of measures ranging from enforcement of NPI, vaccination, and symptomatic and supporting treatment of patients, working with governments, NGOs, development partners, and citizens [27].Vaccine hesitancy, low-risk perception of COVID-19 by citizens, mistrust of government, conspiracy theories, myths, and fake news have weakened compliance and enforcement of COVID-19 preventive measures.
The study described the characteristics of outpatients who presented with ARI to clinics and hospitals in four metropolitan LGAs of Kaduna State, determined the prevalence of ARI among these patients, and evaluated the relationship between ARI and symptoms of depression among the outpatients and a control group.

Study design
We utilized a cross-sectional design, investigated the prevalence of symptoms of depression among outpatients with ARI, and described the characteristics of outpatients with ARI in Kaduna State.

Study setting
Four (4) metropolitan Local Government Areas of Chikun, Igabi, Kaduna North, and Kaduna South were purposefully sampled because they have contributed to >50% of the total COVID-19 burden in Kaduna State since the outset of the pandemic in March 2020.Kaduna State is in Nigeria's Northwestern region, with a projected population of 9.7 million (2006 census) [28].It was the former capital of Northern Nigeria before Independence in 1960 and home to many tribes in Nigeria.Kaduna State has 23 LGAs and 255 wards (the lowest administrative unit).The Infant Mortality rate (170/1000) and the maternal mortality rate (230/100000) are below the national average.The state health insurance scheme has enrolled about 5% of the total population (state employees), and the rest access health services through out-of-pocket expenses.The predominant tribes are Hausa and Fulani ethnic groups.Other ethnic groups are Gwari, Kadara, Bajju, Kataf, etc. Christianity, Islam, and traditional faith are the dominant religions.The state has a boundary with Kano State (north), Plateau and Nassarawa States (south), Bauchi State (east), and NigerState e(west).Kaduna State is an agricultural state and one of Nigeria's leading ginger, maize, and millet producers [28].

Study population
The study population consisted of outpatients who presented with symptoms of ARI to primary, secondary, or tertiary health facilities, both private and public, in the four metropolitan LGAs in the last two weeks before the study and a control group.

Sampling technique
The researcher conducted a stratified random sampling of health facilities (primary, secondary & tertiary), both private and public.The first stratum is the LGA, then the ward (lowest administrative unit), and the type of facility (private or public).The total health facilities in the state range from Primary Health Centre (PHC) (1725), secondary facilities (29), tertiary facilities (6), and private facilities (534).The four metropolitan LGAs accounted for 13% (221) of total PHC, 20% (6) of secondary health facilities, 50% (1) of tertiary health facilities, and 33% (178) of private health facilities.A total of 33 (15%) PHCs, five (83%) secondary health facilities, one (50%) tertiary health facility, and 33 (19%) private health facilities were sampled from the four metropolitan LGAs.The sample distribution was based on probability proportional to size (PPS) (size of respondents depended on the number of outpatients with symptoms of ARI seen by the facility).

Study tools
Symptoms of depression.The researcher and his assistants utilized the Beck Depression Inventory (BDI) to measure the symptoms of depression among outpatients who presented with ARI.The BDI has undergone two major revisions: in 1978 as the BDI-IA and in 1996 as the Beck Depression Inventory-II (BDI-II).The updated BDI-II taps psychological and somatic manifestations of 2-week major depressive episodes, as operationalized in the DSM-IV.9This version was modified to reword and replace some items.Four items of the BDI-IA that proved less sensitive for identification of typical symptoms of severe depressionweight loss, distorted body image, somatic preoccupation, and inability to work-were dropped and replaced by agitation, worthlessness, difficulty concentrating, and energy loss to assess a distinctive degree of intensity of depression.In addition, the items on appetite and sleep change were amended to evaluate the increase and decrease of these depression-related behaviors.Unlike the original version, the BDI-II does not reflect any particular theory of depression [30].
The BDI-II is a relevant psychometric instrument.It has high reliability and capacity to differentiate between depressed and non-depressed subjects and improved concurrent, content, and structural validity.And from available psychometric data, the BDI-II is a cost-effective tool for measuring the severity of depression, with good applicability for research and clinical practice worldwide.The instrument has an internal consistency of 0.9 and retest reliability ranging from 0.73 to 0.96 [30].
ARI. the presence of at least fever and cough and any other symptoms (sneezing, sore throat, headache, body weakness, malaise, dizziness).The ARI questionnaire also explored the duration of symptoms, type of health facility visited by the patient, clinician seen, diagnosis, recovery, and satisfaction with treatment at the health facility.The researcher and his assistants actively searched the health facility outpatients' registers for ARI [11].
Questionnaire.The semi-structured questionnaire has three parts: general information or biodata, a questionnaire on symptoms of depression (BDI), and a questionnaire on ARI.The questionnaire was translated to Hausa (local language) and back-translated to English to ensure internal consistency.The translator is a native Hausa speaker with over 15 years of teaching experience in Hausa and a National Certificate in Education (NCE).The interviewers received intensive 1-day training on the study rationale, questions, design, and tools.
Procedure.The researcher and his assistants administered the questionnaire to the randomly sampled outpatients from the outpatients' register maintained at the health facility.The interviews were conducted at the participants' homes and, in some cases, by telephone in keeping with COVID-19 protocol.The respondents were recruited and interviewed between 14th March and 15 th April 2022.
We compared the study population (outpatients) with the matched control population (size, culture, locality, and socio-economic factors).
Inclusion criteria.All outpatients, 13 years (BDI validated in 13 years and above) and above residents in the four metropolitan LGAs who presented to the health facility in the last two weeks with ARI were sampled for the study.
Exclusion criteria.Outpatients with known depression and patients with debilitating illnesses.
Data collation and statistical analysis.The researchers used the SPSS (Statistical Package for Social Science) in data collation.Descriptive statistics for proportions and measures of central tendencies were calculated.The researcher ran a paired samples t-test and compared the means of the study and control populations at P<0.05.The Pearson's Coefficient of correlations was computed for the measured variable between the two groups.

Ethical consideration
The researchers sought and obtained ethical approval (NHREC/17/03/2018) from the Kaduna State Ministry of Health.

Written informed consent
Only respondents who willingly gave written informed consent participated in the study after a clear protocol explanation.Parents or caregivers provided consent on behalf of minors (<18 years), and assent or cooperation was obtained from the minors before the interview.

Features of respondents presenting with symptoms of acute respiratory infections
The most frequent symptom among those with ARI was sore throat (25%); others were fever (21%), cough (20%), headache (14%), and the minor symptoms are abdominal pain, catarrh, dizziness, heartburn, and nausea (<1%) (Fig 1).The average duration of the symptoms was 3-4 days (46%), symptoms <14 days (93%), and >14 days (7%).The majority of the respondents with symptoms of ARI presented to the Primary Healthcare Centre (PHC) (79%) for treatment.Corollary, many of the respondents who visited PHC were attended to by Community Health Extension Workers (CHEW) (50%), Community Health Officers (CHO) (18%), and at other facilities by medical officers (19%), and least consultant physician (4%).The most typical diagnoses among respondents who presented with symptoms of ARI were malaria (45%) and Typhoid fever (28%), and the least were COVID-19 and diabetes mellitus (<1%) (Fig 2).Most of the respondents who presented with symptoms of ARI were satisfied (97%) with the treatment received at the health facilities visited, and 89% of the respondents who sought treatment recovered after completing their treatment.The average recovery days were 3-4 days (44%), and 10% of the respondents stayed seven days and above before recovery from ARI symptoms.Among the respondents, 31% had a history of a family member presenting with ARI symptoms.Likewise, 35% of the respondents knew somebody outside the family who presented with symptoms of ARI (Table 2).

Association between symptoms of ARI and depression.
The commonest symptoms of depression among the respondents in both case and control were sleep disturbances, feelings of sadness, easy tiredness, and low appetite, of which the majority were female; I don't sleep well (male 38%, female 62%), I feel sad (male 37%, female 63%), easy tiredness (male 33%, female 67%), and low appetite (male 33%, female 67%).
The respondents who were unemployed (33%) and house-wives (30%) accounted for the commonest symptoms of depression (feeling of sadness, easy tiredness, disturbed sleep, and low appetite) observed among all respondents, both those with symptoms of ARI and those without the symptoms of ARI, while government workers (7%) and big-time traders (2%) had the least symptoms of depression.
The respondents who had diabetes and typhoid fever accounted for the most typical symptoms of depression (feeling of sadness, easy tiredness, disturbed sleep, and low appetite) observed among all respondents, both those with symptoms and without symptoms of ARI and those with hypertension, URTI, and RTI had the least symptoms of depression.

Discussion
This study has shown that the likelihood of no symptoms or mild symptoms of depression is commoner among respondents with no symptoms of Acute Respiratory Infection (ARI).Though causality cannot be inferred, the association is statistically significant (see Table 4).However, there was no significant difference between respondents with ARI symptoms and no The symptoms of ARI were prevalent among the respondents who presented as outpatients at private and public health facilities.The most typical diagnoses were malaria and typhoid fever.The most familiar symptoms of ARI are sore throat, fever, and cough.The diagnosis of COVID-19, one of the differential diagnoses of ARI based purely on symptomatology, can be misleading because many common conditions (malaria, typhoid fever) present with similar symptoms.
This study has also shown that the unemployed and house-wives and those with diagnoses of diabetes and typhoid fever accounted for a higher proportion of the symptoms of depression, such as the feeling of sadness, easy tiredness, sleep disturbance, low appetite, and commoner among female than male in both respondents with ARI symptoms and without ARI symptoms.However, this pattern may reflect the higher percentage of females (64%) among the total case and control respondents.These findings are consistent with previous studies that demonstrated a high prevalence of the symptoms of depression and features of other mental illnesses among clients who presented with symptoms of ARI [24].

Local and regional implications
The decline in the incidence of COVID-19 should be sustained through reinforced risk communication, community engagement, and enforcement of non-pharmaceutical interventions, like social distancing, handwashing with soap under running water, and use of facemasks, environmental sanitation, and personal hygiene.The political leadership at the local and regional levels working through the relevant response organs (Nigeria's Presidential Taskforce and African Union's Centre for Disease Control and Prevention) should engage and collaborate with traditional and religious institutions and their leadership, and other professional bodies and institutions to deepen awareness of COVID-19 infections, its transmission, and prevention measures, and clear all myths on COVID-19 vaccination.This engagement will promote the uptake of the COVID-19 vaccine, especially among the elderly and the vulnerable population (those living with co-morbidity, like diabetes and hypertension).
The local and regional leaders should also engage political leaders at all levels through periodic physical and virtual meetings and interactions to identify successes and challenges and provide policy direction, resources, and workforce to overcome the economic, social, medical, and personal losses to the COVID-19 pandemic, especially in developing countries like Nigeria.

International implications
The World Health Organization (WHO) should continue to lead the coordinated response to COVID-19 through collaboration with national governments, development partners, and donors.WHO should sustain her leadership role, policy, technical assistance, research and advocacy, and resource mobilization in the face of the rampaging COVID-19 pandemic.The WHO, working with other development partners and donors, should support low and middleincome countries, especially in Africa and Asia, with policy and technical assistance, free COVID-19 vaccines, PPEs, and financial grants to enable fragile states to cope with the unprecedented economic, social, and personal losses to COVID-19 pandemic.
The one health approach through sustained communication, collaboration, and coordination of human health, animal health, and environmental interventions remains the proven response to the COVID-19 pandemic and other emerging and re-emerging diseases.

Recommendations
The study has shown more respondents with symptoms of ARI visited the Primary Healthcare Centers (PHC), where most health workers have limited skills and training in treating mental illnesses, such as depression.Having psychiatrists, psychologists, and mental health specialists posted to PHCs in developing countries may be challenging; however, the Community Health Officers (CHO) and Community Health Extension Workers (CHEW) can receive sufficient training in mental health to enable them to profile all OPD patients for depression and other mental illnesses and refer clients with symptoms of depression to appropriate facilities for better care.
Establishing a robust, efficient, and effective referral system, with the protocol fully communicated to health workers and managers at the different levels of care, will reduce delays in the referral of clients and improve the overall care of clients with mental illnesses like depression.
The high prevalence of symptoms of depression among those with symptoms of ARI and those without symptoms of ARI demands more attention and resources to diagnose and care for clients with mental illnesses that may be co-morbid with other common conditions, like malaria, typhoid fever, diabetes, hypertension and so forth.The leadership of developing countries should allocate more resources to health and a significant proportion to address the high burden of mental illness that accounts for colossal Disability Adjusted Life Years (DALYs) in most Low-and Middle-Income Countries (LMICs), like Nigeria [31].
The education and sensitization of clients and the public will increase the awareness of symptoms of depression, improve the health-seeking behaviors of the citizens, lead to early presentation to health facilities, and reduce visits to quacks and unlicensed mental health practitioners.

Limitations
The study was cross-sectional, and no causality was inferred.ARI is not a cause of symptoms of depression.The study was conducted in only four (4) out of the 23 LGAs of Kaduna State, though the sample size was significant, and the findings can be generalized to the total population.Some of the BDI items or questionnaires tapped on profoundly personal and relationship experiences that may provoke pain or trauma; though un-intended, the researcher and his assistants obtained informed consent from respondents after counseling and adequately explained the nature, objectives, and scope of the study in the preferred language.Recall bias was considered a limitation as participants were to provide information on the health occurrence in the two weeks before data collection.

The need for further research
Further research is needed to fully explore the relationship between common medical conditions, for example, malaria, typhoid fever, diabetes, and symptoms of depression and other mental health illnesses.The prevalence of other mental illnesses, like anxiety disorders, should be investigated, and results should be disseminated to health workers and managers to guide clients' profiling, care, and management appropriately.

Conclusion
Though symptoms of depression were common among respondents who presented with symptoms of Acute Respiratory Infection (ARI) at the Outpatient Department (OPD), causality cannot be inferred.Many common conditions, like malaria, typhoid fever, diabetes, and hypertension, can manifest with symptoms of depression, and clinicians can miss the diagnosis of mental illness like depression if other distinguishing features of depression are not elicited through detailed history taking, examination, and investigation by qualified and trained health workers.The burden of mental illness, like depression, is enormous and accounts for many Disability Adjusted Life Years (DALYs) in LMICs.More resources, a trained and motivated workforce, and other support to diagnose, care, and manage clients presenting with symptoms of depression and other mental illnesses in private and public health facilities are needed, especially in LMICs.

Fig 1 .
Fig 1. Symptoms of ARI among respondents who presented at the outpatient department of health facility with symptoms of ARI.https://doi.org/10.1371/journal.pone.0288567.g001

Fig 2 .
Fig 2. Diagnosis by clinicians of respondents who presented at the outpatient department of health facility with symptoms of ARI.https://doi.org/10.1371/journal.pone.0288567.g002

Table 4 . A comparison of mean, standard deviation, and P-value scores of respondents on the Beck Depression Inventory and the prevalence of symptoms of depression.
Since the symptoms of depression can manifest in common conditions like malaria, typhoid fever, diabetes, and hypertension, clinicians should widen their scope when profiling clients for the risk of depression.The diagnosis of COVID-19 requires detailed history taking, with particular attention to onset, duration, and severity of symptoms, travel history, and contact with people suffering from symptoms suggestive of COVID-19 or diagnosis of COVID-19.